The goal of this project is to elucidate the regulatory mechanisms in surfactant phospholipid biosynthesis, secretion and re-uptake in type II cells isolated from silica-injured developing and adult lungs. Two populations of type II cells can be isolated from silica-treated adult rats: type IIA cells, similar to type II cells from normal rats, and type IIB cells which are larger, contain more lamellar bodies and have a higher rate of phosphatidylcholine (PC) biosynthesis. Type IIB cells, therefore, provide an interesting system in which to study the regulation of surfactant phospholipid metabolism. The Specific Aims are: 1. To determine the mechanism of increased PC biosynthesis in type IIB cells from adult rats. In particular, we will test the hypothesis that the enhanced PC biosynthesis is mediated by induction of fatty acid biosynthesis. 2. To determine if silica has the same effect in another species, whether two populations of type II cells can be isolated from silica-treated rabbits and whether PC synthesis is increased by the same mechanism in type IIB cells from this species. 3. To determine if newborn and developing lungs respond to silica in the same manner as those of adults. 4. To determine if regulation of PC secretion is disrupted in type IIB cells. 5. To determine if re-uptake of surfactant phospholipids is altered in type IIB cells. The studies will be largely carried out in primary cultures of type II cells and will involve measurements of activities of enzymes of fatty acid and phospholipid biosynthesis, enzyme quantitation by immunotitration, determination of mRNA levels by Northern blotting and measurement of rates of PC secretion as well as uptake from liposomes in the culture medium. The effect of inhibition of fatty acid biosynthesis on the increase in PC biosynthesis will be assessed. The injury resulting from exposure to silica is but one type of lung injury and would not be expected to normally occur in the newborn or developing young animal. Nevertheless, the silica- injured lung provides a model in which to examine how the pulmonary surfactant system responds to an insult. Therefore, this proposal is designed to determine how surfactant metabolism is regulated in type II cells isolated from such lungs. Information obtained in the silica-injured lung model will hopefully be relevant to other kinds of injury to both the adult and developing lung.